Crystal structure of IcaR, a repressor of the TetR family implicated in biofilm formation in staphylococcus epidermidis

Wen Yih Jeng, Tzu Ping Ko, Chia I. Liu, Rey Ting Guo, Chien Liang Liu, Hui Lin Shr, Andrew H J Wang

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Expression of the gene cluster icaADBC is necessary for biofilm production in Staphylococcus epidermidis. The ica operon is negatively controlled by the repressor IcaR. Here, the crystal structure of IcaR was determined and the refined structure revealed a homodimer comprising entirely α-helices, typical of the tetracycline repressor protein family for gene regulations. The N-terminal domain contains a conserved helix-turn-helix DNA-binding motif with some conformational variations, indicating flexibility in this region. The C-terminal domain shows a complementary surface charge distribution about the dyad axis, ideal for efficient and specific dimer formation. The results of the electrophoretic mobility shift assay and isothermal titration calorimetry suggested that a 28 bp core segment of the ica operator is implicated in the cooperative binding of two IcaR dimers on opposite sides of the duplex DNA. Computer modeling based on the known DNA-complex structure of QacR and site-specific mutagenesis experiments showed that direct protein-DNA interactions are mostly conserved, but with slight variations for recognizing the different sequences. By interfering with the binding of IcaR to DNA, aminoglycoside gentamicin and other antibiotics may activate the icaADBC genes and elicit biofilm production in S. epidermidis, and likely S. aureus, as a defense mechanism.

Original languageEnglish
Pages (from-to)1567-1577
Number of pages11
JournalNucleic Acids Research
Volume36
Issue number5
DOIs
Publication statusPublished - Mar 2008
Externally publishedYes

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Iron-Dextran Complex
Staphylococcus epidermidis
Biofilms
DNA
Repressor Proteins
Calorimetry
Nucleotide Motifs
Aminoglycosides
Electrophoretic Mobility Shift Assay
Defense Mechanisms
Operon
Multigene Family
Site-Directed Mutagenesis
Gentamicins
Tetracycline
Genes
Anti-Bacterial Agents
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Crystal structure of IcaR, a repressor of the TetR family implicated in biofilm formation in staphylococcus epidermidis. / Jeng, Wen Yih; Ko, Tzu Ping; Liu, Chia I.; Guo, Rey Ting; Liu, Chien Liang; Shr, Hui Lin; Wang, Andrew H J.

In: Nucleic Acids Research, Vol. 36, No. 5, 03.2008, p. 1567-1577.

Research output: Contribution to journalArticle

Jeng, Wen Yih ; Ko, Tzu Ping ; Liu, Chia I. ; Guo, Rey Ting ; Liu, Chien Liang ; Shr, Hui Lin ; Wang, Andrew H J. / Crystal structure of IcaR, a repressor of the TetR family implicated in biofilm formation in staphylococcus epidermidis. In: Nucleic Acids Research. 2008 ; Vol. 36, No. 5. pp. 1567-1577.
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